We propose to develop and test novel instrumentation for magnetic nanoparticle delivery of therapeutic payloads. The intent of this project is to model and optimize a novel configuration of permanent magnets so as to inject or push the magnetically susceptible composite nanoparticles into target tissues. Current technology can only attract or pull particles towards a magnet pole face. The push method we describe will demonstrate an improvement on current magnetic nanomedicine delivery methods. In particular, it will enable new applications such as treatment of the inner ear, non- invasive injection of drugs to nerves for treatment of intra and post-operative heart atrial fibrillation, safer delivery of drugs to the retina of the eye, and effect wide area 'paint-on'treatment of antibiotic resistant infections, all of which cannot be treated with magnetic drug delivery today due to the strong magnets that would be required on the opposing side of the body to effectively pull the therapeutics in. We propose to design, optimize, and validate the utility of our Magnetic Injector System (MIS) in both a bench top and an animal study. Design and optimization of the configurations will be performed through advanced simulations and optimization techniques. Testing the MIS will be accomplished through magnetic field and force testing apparatus as well as imaging and analysis software that will record the controlled movements of magnetite-containing polymeric nanoparticles on the bench top. Once optimization and testing are performed in-vitro the device will be tested in- vivo, on guinea pig ears with radioisotope conjugated nanoparticles to enable us to quantify the amount of drug delivery that has been achieved. The conclusions of this project will provide the information required to develop clinical adaptations. We have found partners who also see the potential of this technology and are interested in pursuing this idea in further collaborations. Although many of the envisioned clinical applications will require further research to transition the instrument from bench top to bedside, for some applications, notably treatment of the inner ear for sensorineural hearing loss and driving of drugs through the protective layer of methicillin resistant skin infections (MRSA) to kill the underlying bacteria colonies, are amenable to fast transition. Once the instrument has been demonstrated, it could be used as-is in the doctors'office to better treat these ailments - quickly, effectively, and cheaply. PUBLIC HEALTH RELEVANCE (provided by applicant): We propose to develop and optimize a novel instrument to inject or push magnetically active nanoparticle therapies into medically affected tissues. The instrument will not only enhance current nano-therapy practices, but provide a means to new therapies that until now have been impractical or dangerous due to the size of magnets required to implement them. We expect the instrument to work (with properly loaded nanoparticles) to treat sensorineural hearing loss, postoperative atrial fibrillation, MRSA infections, and diabetic retinopathies.